In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine.
In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine.
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DOI：
10.1016/j.yjmcc.2009.01.012
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发表时间：
2009-06
影响因子：
5
通讯作者：
Brookes, Paul S.
中科院分区：
文献类型：
--
作者：
Nadtochiy, Sergiy M.;Burwell, Lindsay S.;Ingraham, Christopher A.;Spencer, Cody M.;Friedman, Alan E.;Pinkert, Carl A.;Brookes, Paul S.
可逆的S-亚硝化和线粒体复合物I的抑制是心肌保护的潜在机制，由缺血预处理（IPC），S-亚硝基硫醇和亚硝酸盐招募。以前，为了利用这一机制，开发了线粒体S-亚硝基化剂S-亚硝基-2-巯基丙酰甘氨酸（SNO-MPG），并保护灌注心脏和分离的心肌细胞免受缺血-再灌注（IR）损伤。在本研究中，采用小鼠左前降支冠状动脉（LAD）闭塞的IR损伤模型，以确定SNO-MPG在体内的保护作用。在闭塞前30分钟腹腔内给予1 mg/kg SNO-MPG，在闭塞30分钟加2或24小时再灌注后，显著减少心肌梗死并改善EKG参数。SNO-MPG的保护程度与IPC相同，并且在再灌注时给药时也具有明显的保护作用。线粒体蛋白S-亚硝基硫醇含量的增加，并抑制复合物I，这两个都被逆转后2小时。再灌注。最后，来自在复合物I NDUSF 4亚基中具有杂合突变的小鼠的心脏对SNO-MPG或IPC的保护是难治的，这表明能够可逆抑制的全功能复合物I对于心脏保护是至关重要的。总体而言，这些结果与线粒体S-亚硝化和复合物I抑制在IPC和SNO-MPG体内心脏保护机制中的作用一致。
The reversible S-nitrosation and inhibition of mitochondrial complex I is a potential mechanism of cardioprotection, recruited by ischemic preconditioning (IPC), S-nitrosothiols, and nitrite. Previously, to exploit this mechanism, the mitochondrial S-nitrosating agent S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) was developed, and protected perfused hearts and isolated cardiomyocytes against ischemia-reperfusion (IR) injury. In the present study, the murine left anterior descending coronary artery (LAD) occlusion model of IR injury was employed, to determine the protective efficacy of SNO-MPG in vivo. Intraperitoneal administration of 1 mg/kg SNO-MPG, 30 min. prior to occlusion, significantly reduced myocardial infarction and improved EKG parameters, following 30 min. occlusion plus 2 or 24 hr. reperfusion. SNO-MPG protected to the same degree as IPC, and notably was also protective when administered at reperfusion. Cardioprotection was accompanied by increased mitochondrial protein S-nitrosothiol content, and inhibition of complex I, both of which were reversed after 2 hr. reperfusion. Finally, hearts from mice harboring a heterozygous mutation in the complex I NDUSF4 subunit were refractory to protection by either SNO-MPG or IPC, suggesting that a fully functional complex I, capable of reversible inhibition is critical for cardioprotection. Overall, these results are consistent with a role for mitochondrial S-nitrosation and complex I inhibition in the cardioprotective mechanism of IPC and SNO-MPG in vivo.
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影响因子：
10.8
作者：
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